Targeting Spike‐ACE2 Interface of SARS‐CoV‐2 and its Omicron Variant: A Comparative Screening of Potential Inhibitors for Existing and Anticipating Variants Using Molecular Modelling Approach

Abstract

AbstractThe recent COVID pandemic has shown major impact on public health and economic crisis. Despite the development of many vaccines and drugs against the severe acute respiratory syndrome (SARS) coronavirus 2, the pandemic still persists. The continued spread of the virus is largely driven by the emergence of viral variants such as α, β, γ, delta, epsilon spike, omicron and its subvariants (BA.1,2,3) which can evade the current vaccines through mutations in the spike protein.[1] For instance, spike to omicron has modifications at different mutations (D405N, K417N, S477N, E484A, Q493R, N501Y, Y505H).[1b] These mutations will affect functional properties and hence may alter the specificity towards potential drug candidates. Therefore, it is important to understand the role of these mutations on interactions with existing drug candidates. In this study, we focus on the two forms of SARS‐CoV‐2, such as wild‐type spike and omicron and unveil their interactions with different drugs. For this purpose, we have taken about hundred drugs categorised in twelve groups of anticancer, natural products, enzyme inhibitors, antivirals, antioxidants, anti‐bacterials, anti‐malarials, antidiabetics, antimicrobials, anti‐inflammatory, antifungals and other drugs. We used in‐silico methods to understand the effect of these drug molecules on wild type and omicron spike RBD at the interface of ACE2 enzyme. Based on molecular docking results, we have chosen 7 best docked compounds and studied their interaction patterns in detail by molecular dynamics simulation.